Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel.
DRUG DELIVERY(2016)
摘要
Context: As a glucocorticoid drug, dexamethasone has good therapeutic effects for ulcerative colitis. pH-sensitive hydrogels could make conventional changes of volume in response with different pH values. Meanwhile, they could load drugs depending on its internal three-dimensional network structure. Objective: Appropriate methods were used to improve the drug-loading capacity of hydrogel and exploring the colon-targeting character of dexamethasone hydrogel. Materials and methods: Different solvents (ethanol and 1,2-propanediol) were employed to dissolve dexamethasone as well as hydrogel monomer materials (poly(ethylene glycol) methyl ether (MPEG)-poly(lactide acid)-acryloyl chloride macromonomer, itaconic acid (IA) and MPEG-methacrylate), then mixing them together to prepare hydrogel through the heat-initiated free radical polymerization method. Differential scanning calorimetry and X-ray diffraction methods were used to verify whether dexamethasone was loaded into hydrogels. In vitro drug release behavior and in vivo pharmacokinetic study were also investigated in detail. Results: Dexamethasone was successfully loaded into hydrogel, and its loading capacity was improved (5mg/g). Both the in vitro release study and the in vivo pharmacokinetic study showed the good colon-targeting character of the pH-sensitive P(LE-IA-MEG) hydrogel (T-max=1.0h, C-max=2.16 mu g/ml of dexamethasone; T-max=3.9h, C-max=0.43 mu g/ml of dexamethasone hydrogel). Discussion: Dexamethasone could be targeted to the colon site by P(LE-IA-MEG) hydrogel, thereby improving its therapeutic effect and reduce its side effects. Conclusion: P(LE-IA-MEG) hydrogel might have great potential application in colon-targeted drug delivery systems.
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关键词
Dexamethasone,drug-loading,in vitro drug release study,in vivo pharmacokinetic study,pH-sensitive
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